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https://www.readbyqxmd.com/read/29780562/kinetic-studies-on-strand-displacement-in-de-novo-designed-parallel-heterodimeric-coiled-coils
#1
Mike C Groth, W Mathis Rink, Nils F Meyer, Franziska Thomas
Among the protein folding motifs, which are accessible by de novo design, the parallel heterodimeric coiled coil is most frequently used in bioinspired applications and chemical biology in general. This is due to the straightforward sequence-to-structure relationships, which it has in common with all coiled-coil motifs, and the heterospecificity, which allows control of association. Whereas much focus was laid on designing orthogonal coiled coils, systematic studies on controlling association, for instance by strand displacement, are rare...
May 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29779879/the-xmap215-ortholog-alp14-promotes-microtubule-nucleation-in-fission-yeast
#2
Ignacio Flor-Parra, Ana Belén Iglesias-Romero, Fred Chang
The organization and number of microtubules (MTs) in a cell depend on the proper regulation of MT nucleation. Currently, the mechanism of nucleation is the most poorly understood aspect of MT dynamics. XMAP215/chTOG/Alp14/Stu2 proteins are MT polymerases that stimulate MT polymerization at MT plus ends by binding and releasing tubulin dimers. Although these proteins also localize to MT organizing centers and have nucleating activity in vitro, it is not yet clear whether these proteins participate in MT nucleation in vivo...
May 10, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29771510/relevance-of-the-speed-and-direction-of-pulling-in-simple-modular-proteins
#3
Carlos A Plata, Zackary N Scholl, Piotr E Marszalek, Antonio Prados
A theoretical framework capable of predicting the first unit that unfolds in pulled modular proteins has been recently introduced, for "fast enough" pulling velocities. Within this picture, we investigate the unfolding pathway in a chain of identical units and predict that the module closest to the pulled end opens first. Steered molecular dynamics of a simple construct, specifically a chain composed of two coiled-coil motives, shows that this is indeed the case. Notwithstanding, the unfolding behavior strongly depends on the terminus (C or N) from which this homopolyprotein is pulled...
May 17, 2018: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/29771498/structure-and-function-of-the-transmembrane-domain-of-nsas-an-antibiotic-sensing-histidine-kinase-in-s-aureus
#4
Manasi P Bhate, Thomas Lemmin, Georg Kuenze, Bruk Mensa, Soumya Ganguly, Jason Peters, Nathan Schmidt, Jeffrey G Pelton, Carol Gross, Jens Meiler, William F DeGrado
NsaS is one of four intramembrane histidine kinases (HKs) in Staphylococcus aureus that mediate the pathogen's response to membrane active antimicrobials and human innate immunity. We describe the first integrative structural study of NsaS using a combination of solution state NMR spectroscopy, chemical-crosslinking, molecular modeling and dynamics. Three key structural features emerge: First, NsaS has a short N-terminal amphiphilic helix that anchors its transmembrane (TM) bundle into the inner leaflet of the membrane such that it might sense neighboring proteins or membrane deformations...
May 17, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29769011/evolving-strategies-for-the-treatment-of-t-cell-lymphoma-a-systematic-review-and-recent-patents
#5
Kamel Laribi, Mustapha Alani, Catherine Truong, Alix Baugier de Materre
OBJECTIVE: Mature T-cell lymphomas are a heterogeneous group of T-cell malignancies with a poor outcome. The discovery of new molecular biomarkers has led to the emergence of new drugs in recent years that target various signaling pathways. METHOD: We examined all pertinent published patents through 2015 that analyzed novel methods for the diagnosis and treatment of T cell lymphoma, as well as related published and unpublished studies. Selection criteria were established before data collection...
May 16, 2018: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29765813/isolation-and-characterization-of-fusarium-wilt-resistance-gene-analogs-in-radish
#6
Xiaona Yu, Dong Hyun Kang, Su Ryun Choi, Yinbo Ma, Lu Lu, Sang Heon Oh, Sushil Satish Chhapekar, Yong Pyo Lim
The resistance gene analog (RGA)-based marker strategy is an effective supplement for current marker reservoir of radish disease-resistance breeding. In this study, we identified RGAs based on the conserved nucleotide-binding site (NBS) and S-receptor-like kinase (SRLK) domains. A total of 68 NBS-RGAs and 46 SRLK-RGAs were isolated from two FW-resistant radish inbred lines, B2 and YR31, and one susceptible line, YR15. A BLASTx search revealed that the NBS-RGAs contained six conserved motifs (i.e., P loop, RNBS-A, Kinase-2, RNBS-B, RNBS-C, and GLPL) and the SRLK-RGAs, contained two conserved motifs (i...
May 2018: 3 Biotech
https://www.readbyqxmd.com/read/29765375/functional-alleles-of-chicken-bg-genes-members-of-the-butyrophilin-gene-family-in-peripheral-t-cells
#7
Lei Chen, Michaela Fakiola, Karen Staines, Colin Butter, Jim Kaufman
γδ T cells recognize a wide variety of ligands in mammals, among them members of the butyrophilin (BTN) family. Nothing is known about γδ T cell ligands in chickens, despite there being many such cells in blood and lymphoid tissues, as well as in mucosal surfaces. The major histocompatibility complex (MHC) of chickens was discovered because of polymorphic BG genes, part of the BTN family. All but two BG genes are located in the BG region, oriented head-to-tail so that unequal crossing-over has led to copy number variation (CNV) as well as hybrid (chimeric) genes, making it difficult to identify true alleles...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29762679/spatial-control-of-cell-envelope-biosynthesis-in-mycobacteria
#8
Julia Puffal, Alam García-Heredia, Kathryn C Rahlwes, M Sloan Siegrist, Yasu S Morita
The mycobacterial cell envelope is a complex multilayered structure that provides the strength to the rod-shaped cell and creates the permeability barrier against antibiotics and host immune attack. In this review, we will discuss the spatial coordination of cell envelope biosynthesis and how plasma membrane compartmentalization plays a role in this process. The spatial organization of cell envelope biosynthetic enzymes as well as other membrane-associated proteins is crucial for cellular processes such as polar growth and midcell septum formation...
June 1, 2018: Pathogens and Disease
https://www.readbyqxmd.com/read/29761578/identification-of-the-coiled-coil-domain-as-an-essential-mbd3-element-for-preserving-lineage-commitment-potential-of-embryonic-stem-cells
#9
Masataka Hirasaki, Atsushi Ueda, Masamitsu N Asaka, Kousuke Uranishi, Ayumu Suzuki, Masakazu Kohda, Yosuke Mizuno, Yasushi Okazaki, Masazumi Nishimoto, Jafar Sharif, Haruhiko Koseki, Akihiko Okuda
Embryonic stem cells (ESCs) exhibit two salient features beneficial for regenerative medicine: unlimited self-renewal and pluripotency. Methyl-CpG-binding domain protein 3 (Mbd3), a scaffolding component of the nucleosome remodeling deacetylase complex, is a specific regulator of pluripotency, as ESCs lacking Mbd3 are defective for lineage commitment potential but retain normal self-renewal properties. However, functional similarities and dissimilarities among the three Mbd3 isoforms (a, b, and c) have not been intensively explored...
May 15, 2018: Stem Cells
https://www.readbyqxmd.com/read/29761210/biochemical-properties-of-bacterial-reverse-transcriptase-related-rvt-gene-products-multimerization-protein-priming-and-nucleotide-preference
#10
Irina A Yushenova, Irina R Arkhipova
Cellular reverse transcriptase-related (rvt) genes represent a novel class of reverse transcriptases (RTs), which are only distantly related to RTs of retrotransposons and retroviruses, but, similarly to telomerase RTs, are immobilized in the genome as single-copy genes. They have been preserved by natural selection throughout the evolutionary history of large taxonomic groups, including most fungi, a few plants and invertebrates, and even certain bacteria, being the only RTs present across different domains of life...
May 14, 2018: Current Genetics
https://www.readbyqxmd.com/read/29760063/elastic-coupling-power-stroke-mechanism-of-the-f-1-atpase-molecular-motor
#11
James L Martin, Robert Ishmukhametov, David Spetzler, Tassilo Hornung, Wayne D Frasch
The angular velocity profile of the 120° F1 -ATPase power stroke was resolved as a function of temperature from 16.3 to 44.6 °C using a ΔμATP = -31.25 k B T at a time resolution of 10 μs. Angular velocities during the first 60° of the power stroke (phase 1) varied inversely with temperature, resulting in negative activation energies with a parabolic dependence. This is direct evidence that phase 1 rotation derives from elastic energy (spring constant, κ = 50 k B T ·rad-2 ). Phase 2 of the power stroke had an enthalpic component indicating that additional energy input occurred to enable the γ-subunit to overcome energy stored by the spring after rotating beyond its 34° equilibrium position...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29758162/tuning-liposome-membrane-permeability-by-competitive-coiled-coil-heterodimerization-and-heterodimer-exchange
#12
Camilla Skyttner, Karin Enander, Christopher Aronsson, Daniel Aili
Membrane active peptides that enable triggered release of liposomal cargo is of large interest for development of liposome-based drug delivery systems but require peptide-lipid membrane interactions that are highly defined and tunable. To this end, we have explored the possibility to use the competing interactions between membrane partitioning and heterodimerization and folding of a set of four different de novo designed coiled coil peptides. Covalent conjugation of the cationic peptides triggered rapid destabilization of membrane integrity and release of encapsulated species...
May 14, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29754715/assembly-kinetics-of-vimentin-tetramers-to-unit-length-filaments-a-stopped-flow-study
#13
Norbert Mücke, Lara Kämmerer, Stefan Winheim, Robert Kirmse, Jan Krieger, Maria Mildenberger, Jochen Baßler, Ed Hurt, Wolfgang H Goldmann, Ueli Aebi, Katalin Toth, Jörg Langowski, Harald Herrmann
Intermediate filaments (IFs) are principal components of the cytoskeleton, a dynamic integrated system of structural proteins that provides the functional architecture of metazoan cells. They are major contributors to the elasticity of cells and tissues due to their high mechanical stability and intrinsic flexibility. The basic building block for the assembly of IFs is a rod-like, 60-nm-long tetrameric complex made from two antiparallel, half-staggered coiled coils. In low ionic strength, tetramers form stable complexes that rapidly assemble into filaments upon raising the ionic strength...
May 10, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29753317/long-noncoding-rna-dancr-working-as-a-competitive-endogenous-rna-promotes-rock1-mediated-proliferation-and-metastasis-via-decoying-of-mir-335-5p-and-mir-1972-in-osteosarcoma
#14
Yong Wang, Xiandong Zeng, Ningning Wang, Wei Zhao, Xi Zhang, Songling Teng, Yueyan Zhang, Zhi Lu
BACKGROUND: Accumulating evidences indicate that non-coding RNAs (ncRNAs) including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) acting as crucial regulators in osteosarcoma (OS). Previously, we reported that Rho associated coiled-coil containing protein kinase 1 (ROCK1), a metastatic-related gene was negatively regulated by microRNA-335-5p (miR-335-5p) and work as an oncogene in osteosarcoma. Whether any long non-coding RNAs participate in the upstream of miR-335-5p/ROCK1 axial remains unclear...
May 12, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29752437/caspase-mediated-cleavage-of-the-centrosomal-proteins-during-apoptosis
#15
Mi Young Seo, Kunsoo Rhee
The centrosome is the major microtubule-organizing center and plays important roles in intracellular transport, cellular morphology, and motility. In mitotic cells, centrosomes function as spindle poles to pull a set of chromosomes into daughter cells. In quiescent cells, primary cilia are originated from the centrosomes. Given its involvement in various cellular processes, it is little surprising that the organelle would also participate in apoptotic events. However, it remains elusive how the centrosome changes in structure and organization during apoptosis...
May 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29752403/cryo-em-structure-of-the-cytoplasmic-domain-of-murine-transient-receptor-potential-cation-channel-subfamily-c-member-6-trpc6
#16
Caleigh M Azumaya, Francisco Sierra-Valdez, Julio F Cordero-Morales, Terunaga Nakagawa
The kidney maintains the internal milieu by regulating the retention and excretion of proteins, ions, and small molecules. The glomerular podocyte forms the slit diaphragm of the ultrafiltration filter, whose damage leads to progressive kidney failure and focal segmental glomerulosclerosis (FSGS). The canonical transient receptor potential 6 (TRPC6) ion channel is expressed in the podocyte and mutations in its cytoplasmic domain cause FSGS in humans. In vitro evaluation of disease-causing mutations in TRPC6 has revealed that these genetic alterations result in abnormal ion channel gating...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29749507/identification-of-chchd2-mutations-in-patients-with-alzheimer-s-disease-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia-in-china
#17
Xixi Liu, Bin Jiao, Weiwei Zhang, Tingting Xiao, Lihua Hou, Chuzheng Pan, Beisha Tang, Lu Shen
Recently, the coiled‑coil‑helix‑coiled‑coil‑helix domain 2 (CHCHD2) gene was identified as a possible causative gene for Parkinson's disease (PD). Three other neurodegenerative diseases, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), share significant overlaps with PD in clinical phenotypes, pathological features and genetic heredities, and it is still unclear whether CHCHD2 variants could explain these three diseases. The present study screened all exons of the CHCHD2 gene in a total of 780 patients (511 AD, 181 ALS and 88 FTD) and 500 healthy controls from the Chinese Han population...
May 3, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29748388/the-kinetochore-proteins-cenp-e-and-cenp-f-directly-and-specifically-interact-with-distinct-bub-mitotic-checkpoint-ser-thr-kinases
#18
Giuseppe Ciossani, Katharina Overlack, Arsen Petrovic, Pim J Huis In 't Veld, Carolin Koerner, Sabine Wohlgemuth, Stefano Maffini, Andrea Musacchio
The segregation of chromosomes during cell division relies on the function of the kinetochores, protein complexes that physically connect chromosomes with microtubules of the spindle. The metazoan proteins, centromere protein E (CENP-E) and CENP-F, are components of a fibrous layer of mitotic kinetochores named the corona. Several of their features suggest that CENP-E and CENP-F are paralogs: they are very large (comprising approximately 2700 and 3200 residues, respectively), contain abundant predicted coiled-coil structures, are C-terminally prenylated, and are endowed with microtubule-binding sites at their termini...
May 10, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29747217/fyco1-mediates-clearance-of-%C3%AE-synuclein-aggregates-through-a-rab7-dependent-mechanism
#19
Theodora Saridaki, Markus Nippold, Elisabeth Dinter, Andreas Roos, Leonie Diederichs, Luisa Fensky, Jörg B Schulz, Björn H Falkenburger
Parkinson disease can be caused by mutations in the α-synuclein gene and is characterized by aggregates of α-synuclein protein. We have previously shown that overexpression of the small GTPase Rab7 can induce clearance of α-synuclein aggregates. In this study, we investigate which Rab7 effectors mediate this effect. To model Parkinson disease we expressed the pathogenic A53T mutant of α-synuclein in HEK293T cells and Drosophila melanogaster. We tested the Rab7 effectors FYVE and coiled-coil domain-containing protein 1 (FYCO1) and Rab-interacting lysosomal protein (RILP)...
May 10, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29747011/molecular-characterization-of-rhodeus-uyekii-tripartite-motif-protein-1-trim1-involved-in-ifn-%C3%AE-lps-induced-nf-%C3%AE%C2%BAb-signaling
#20
Julan Kim, Ju-Won Kim, Dong-Gyun Kim, Bo-Hye Nam, Young-Ok Kim, Jung Youn Park, Hee Jeong Kong
The tripartite motif-containing (TRIM) proteins are involved in a wide range of cellular processes, and the role of TRIM1 in immunity has been explored. However, fundamental studies on fish TRIM1 are lacking. In this study, we cloned and characterized TRIM1 cDNA from the Korean rose bitterling, Rhodeus uyekii (RuTRIM1). Two RuTRIM1 isoforms (RuTRIM1-X1 and RuTRIM1-X2) were identified. The coding sequence (CDS) of RuTRIM1-X1 comprised 2157 bp encoding a 718-aa protein, and the CDS of RuTRIM1-X2 comprised 1929 bp encoding a 642-aa protein...
May 7, 2018: Fish & Shellfish Immunology
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